Respiratory syncytial virus (RSV) causes the majority of cases of bronchiolitis and acute lower respiratory tract infection in infants and young children and is also a serious threat to immunocompromised individuals and the elderly.1-5 Hospitalization in the U.S. for RSV-associated infection in pediatric patients costs over 300 million dollars annually,6 and no effective vaccine is currently available. Furthermore, the commercial vaccine palivizumab, only used for high-risk infants, is very expensive and its accessibility is problematic in third world countries.9 The lack of both a vaccine and a cost-effective antiviral treatment for children, the elderly, and immunocompromised patients has created an urgent need for the development of new methodologies for RSV treatment worldwide.
Since the market approval of Palivizumab9-11 (a prophylaxis given to high risk individuals that utilizes a monoclonal antibody that binds to the antigenic site of the RSV F protein and blocks virus entry at the initial stage of infection), several independent studies have focused on the design of inhibitors of the RSV F fusion protein.7,8 Research is also being done to test small-molecule inhibitors3 and RSV F inhibitor peptides12 targeting heptad repeat (HR) domains within the fusion protein combined with biocompatible nanomaterials such as chitosan for targeted delivery.1 Recent structural studies have demonstrated how small synthesized peptides can bind to a site on the F protein where the six-helix bundles are formed by the interaction of HR1 and HR213,14 and block this interaction.3 These peptides contain a sequence of amino acids that are part of the heptad repeat sequence that specifically binds to the HR2 domain of the F protein through coiled-coiled interactions; such binding prevents fusion of the virus with the host cell membrane.2,3 A major drawback of this antiviral strategy, however, is that the peptides are rapidly degraded by proteases in the body, thus requiring high doses to reduce infection. Moreover, the short half-life of peptides in the cells makes therapeutic use difficult. Therefore, prolonging the activity of such peptides using a delivery platform that delays the interaction of proteases with the peptides is desired.